Requirement of NF-kappaB/Rel for the development of hair follicles and other epidermal appendices.
NF-kappaB/Rel transcription factors and IkappaB kinases (IKK) are essential for inflammation and immune responses, but also for bone-morphogenesis, skin proliferation and differentiation. Determining their other functions has previously been impossible, owing to embryonic lethality of NF-kappaB/Rel or IKK-deficient animals. Using a gene targeting approach we have ubiquitously expressed an NF-kappaB super-repressor to investigate NF-kappaB functions in the adult. Mice with suppressed NF-kappaB revealed defective early morphogenesis of hair follicles, exocrine glands and teeth, identical to Eda (tabby) and Edar (downless) mutant mice. These affected epithelial appendices normally display high NF-kappaB activity, suppression of which resulted in increased apoptosis, indicating that NF-kappaB acts as a survival factor downstream of the tumor necrosis factor receptor family member EDAR. Furthermore, NF-kappaB is required for peripheral lymph node formation and macrophage function.
Pubmed ID: 11585809 RIS Download
Animals | Apoptosis | Deafness | Eccrine Glands | Ectodysplasins | Edar Receptor | Epidermis | Exocrine Glands | Hair Follicle | Hepatocytes | I-kappa B Proteins | Lymphatic System | Macrophages | Membrane Proteins | Mice | Mice, Inbred C57BL | Mice, Transgenic | Mutation | NF-kappa B | Oncogene Proteins v-rel | Otitis Media | Receptors, Ectodysplasin | Receptors, Tumor Necrosis Factor | Signal Transduction | Tooth